Pre-operative endometrial thinning agents before hysteroscopic surgery for heavy menstrual bleeding

Menorrhagia is one of the most common reasons for pre-menopausal women to be referred to a gynaecologist. Although medical therapy is generally the first approach, many will eventually require or request a hysterectomy. Hysterectomy is associated with a significant in-patient hospital stay and a period of convalescence that makes it an unattractive and unnecessarily invasive option for many women. Hysteroscopic endometrial ablation or resection offers a day-case surgical alternative to hysterectomy for these women. It is also a cheaper procedure than hysterectomy. Complete endometrial removal or destruction is one of the most important determinants of treatment success. Therefore surgery will be most effective if undertaken when endometrial thickness is less than 4mm, in the immediate post-menstrual phase, however there are often difficulties in reliably arranging surgery for this time. The other option is the use of hormonal agents which induce endometrial thinning or atrophy prior to surgery. The most commonly evaluated agents have been goserelin (a GnRH analogue) and danazol. Progestogens and other GnRH analogues have also been studied although less data are available. It has been suggested that the use of these agents, particularly GnRH analogues, will reduce operating time, improve the intra-uterine operating environment, and reduce distension medium absorption (this is the fluid used to distend the uterine cavity during surgery).

To investigate the effectiveness of gonadotrophin-releasing hormone (GnRH) analogues, danazol, and progestogens, when used for endometrial thinning prior to hysteroscopic surgery for menorrhagia, in improving the intra-uterine operating environment and treatment outcome after surgery.

The Menstrual Disorders and Subfertility Group search strategy (see Review Group details) was used to identify randomised trials that had compared the use of these drugs with either each other, or placebo, or no pre-operative treatment.

Trials were included if they compared the effects of these agents with each other, or with placebo or no treatment on relevant intra-operative and post-operative treatment outcomes. Only randomised studies were included in this review.

Eight studies met the inclusion criteria for this review. Four studies compared goserelin (a GnRH analogue) with no treatment or placebo. Three studies compared goserelin with danazol. One study compared progestogens, danazol and triptorelin (a GnRH analogue) with no treatment. Data was extracted independently by two reviewers. A third reviewer checked data extraction for accuracy and wrote to authors where relevant data was missing or unclear. Intra-operative parameters included endometrial thickness, duration of surgery, ease of surgery, distension medium absorption and complication rate. Post-operative outcomes compared were the proportion of women with amenorrhoea, post-operative menstrual loss and dysmenorrhoea, and the need for further surgery. Data on side-effects were also recorded.

When compared with no treatment GnRH analogues are associated with a shorter duration of surgery, greater ease of surgery and a higher rate of post-operative amenorrhoea. Post-operative dysmenorrhoea also appears to be reduced. The use of GnRH analogues has no effect on intra-operative complication rates and patient satisfaction with this surgery is high irrespective of the use of any pre-operative endometrial thinning agent. GnRH analogues produce more consistent endometrial atrophy than danazol. For other intra-operative and post-operative outcomes any differences are minimal. Both GnRH analogues and danazol produce side-effects in a significant proportion of women, though few studies have reported these in detail. Little randomised data is available to assess the effectiveness of progestogens as endometrial thinning agents and the effect of any thinning agent